The objective of this project is to provide a broad base of information on the expected response of normal and tumor tissues following exposure to negative pi mesons (pions), such that clinical trials of pion radiotherapy for patients with extensive cancer can be designed most effectively. This renewal application proposes methods of improving biomedical channel operations at the Los Alamos Scientific Laboratory Meson Physics Facility (LAMPF) for delivery of a beam that can be tailored to a tumor volume of arbitrary shape and size; refinement of dosimetric techniques; determination of dosimetric factors associated with body inhomogeneities; and development and refinement of devices and procedures for patient treatment support (e.g., localization, treatment planning, immobilization, simulation, and set-up and treatment verification). Biological studies will be conducted to determine injury to normal and tumor tissues in the peak region, the sparing factor for normal tissues adjacent to the tumor volume and/or in the plateau beam path; optimal fractionation schedules; isoeffect characteristics; and reasons for observed changes in therapeutic effect.